BIOMD0000000398
type: SBMLModel
parameter: 659133
reaction: 658991
parameter: 659106
reaction: 658928
species: 658737
species: 658583
is: MODEL1111020000
time units: 949038
reaction: 658969
parameter: 659064
reaction: 659010
species: 658431
parameter: 659076
species: 658481
species: 658515
species: 658363
parameter: 659115
reaction: 659030
parameter: 659088
substance units: 142808
parameter: 659067
parameter: 659154
reaction: 658828
curated: true
parameter: 659127
species: 658345
parameter: 659160
parameter: 659166
reaction: 658886
parameter: 659139
parameter: 659112
parameter: 659118
species: 658617
parameter: 659172
parameter: 659145
parameter: 659151
name: Sivakumar2011_NeuralStemCellDifferentiation_Crosstalk
parameter: 659124
species: 658787
parameter: 659163
compartment: 658329
parameter: 659136
is described by: http://identifiers.org/pubmed/21978399
parameter: 659148
species: 658533
is version of: GO:0007173
is version of: GO:0060070
species: 658447
is version of: GO:0007219
species: 658600
parameter: 659079
species: 658668
species: 658651
reaction: 658849
parameter: 659073
parameter: 659157
species: 658702
species: 658549
parameter: 659085
parameter: 659169
reaction: 658867
notes: This model is from the article: A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways. Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S. OMICS 2011 Oct;15(10):729-37. 21978399 , Abstract: The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to in fluence cell fate specification in the developing nervous system. Here we attempt ed to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Ou r model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E (spl)] genes and enhancement of Shh target genes by a SAG agonist that were effec tively demonstrated computationally and were consistent with experimental studies . However, in the case of model simulation of Wnt and EGF pathways, the model net work did not supply any concurrent results with experimental data despite the fac t that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species conne cted by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted th e regulation of a single target gene, Hes-1, based on drug-induced simulations. T hese simulations provided results that matched with experimental studies. Therefo re, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferati on, and differentiation during mammalian central nervous system development. To o ur knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores t he flow of positive and negative regulatory signals modulated by drugs.
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species: 658380
species: 658464
species: 658414
area units: 498119
volume units: 142784
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length unit: length

659133
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constant: true
value: 1.0

658991
type: Reaction
kinetic law: 247810
product: 247798
reactant: 247786
notes: mass action rate law for first order forward, first order reverse, reversible reactions, continuous scheme
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reversible: true

247798
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658464
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constant: false
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name: Hes-1

658329
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constant: true
size: 1.0
spatial dimensions: 3.0
name: nucleus

247786
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658753
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name: Beta-catenin

658326
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659106
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constant: true
value: 1.0

658928
type: Reaction
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product: 247630
reactant: 247618
reactant: 247606
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
fast: false
reversible: true

247630
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name: Complex Wnt-Frzzl

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name: EGFR

658969
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modifier: 247762
reversible: true
reactant: 247726
fast: false
product: 247738
reactant: 247714
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
modifier: 247750

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name: Complex Dishevelled-FRAT-CK2

247726
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247738
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name: Complex GSK3B-Bcatenin

247714
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name: 6 bromoindirubin 3`oxime

659064
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constant: true
value: 1.0

659010
type: Reaction
notes: kinetics of non-modulated unireactant enzymes
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reversible: true
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fast: false
reactant: 247822
modifier: 247858

658515
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constant: false
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initial amount: 0.0
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name: Complex Shh Ptch1

247834
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658533
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658549
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658431
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name: RBP-jk

659076
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constant: true
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658481
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is version of: Q15465
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boundary condition: false
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initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: Shh

658363
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constant: false
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initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: Notch

659115
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constant: true
value: 1.0

659030
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kinetic law: 247918
modifier: 247906
product: 247894
reactant: 247882
notes: mass action rate law for first order forward, first order reverse, reversible reactions, continuous scheme
fast: false
reversible: true

247894
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species: 658464

247882
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659088
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constant: true
value: 1.0

659067
type: Parameter
constant: true
value: 1.0

659154
type: Parameter
constant: true
value: 1.0

658828
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kinetic law: 247415
product: 247403
reactant: 247391
reactant: 247379
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
fast: false
reversible: true

247403
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658447
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name: Complex NICD-RBP

247391
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247379
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658345
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initial concentration: NaN
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name: NICD

659127
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constant: true
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659160
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constant: true
value: 1.0

659166
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constant: true
value: 1.0

658886
type: Reaction
kinetic law: 247558
product: 247534
reactant: 247510
fast: false
reactant: 247522
reversible: true
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
modifier: 247546

247534
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species: 658600

658600
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constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 658326
name: Complex EGF-EGFR

247510
type: SpeciesReference
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species: 658567

658567
type: Species
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constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: EGF

247522
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species: 658583

658617
type: Species
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constant: false
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initial concentration: NaN
initial amount: 100.0
in compartment: 658326
name: Erlotinib

659139
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constant: true
value: 1.0

659112
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constant: true
value: 1.0

659118
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constant: true
value: 1.0

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constant: true
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659124
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659136
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659148
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659079
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constant: true
value: 1.0

658849
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product: 247438
reactant: 247426
notes: mass action rate law for first order forward, first order reverse, reversible reactions, continuous scheme
fast: false
reversible: true

247438
type: SpeciesReference
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species: 658464

247426
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species: 658447

659073
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constant: true
value: 1.0

659157
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constant: true
value: 1.0

658702
type: Species
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constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: FRAT-CK2

659085
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constant: true
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659169
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constant: true
value: 1.0

658867
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product: 247486
reactant: 247474
reactant: 247462
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
fast: false
reversible: true

247486
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species: 658515

247474
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species: 658498

658498
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constant: false
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initial concentration: NaN
initial amount: 5.0
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name: Ptch1

247462
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species: 658481

658948
type: Reaction
reversible: true
reactant: 247654
product: 247678
reactant: 247666
modifier: 247690
fast: false
notes: reversible rapid-equilibrium random order ternary-complex mechanism with one product
kinetic law: 247702

247654
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species: 658686

658686
type: Species
is homolog to: Q86TH3
constant: false
boundary condition: false
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initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: Dishevelled

247678
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species: 658719

247666
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species: 658702

659100
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constant: true
value: 1.0

659097
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constant: true
value: 1.0

658806
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reactant: 247307
reversible: true
modifier: 247343
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product: 247331
fast: false
product: 247319
modifier: 247355
notes: reversible thermodynamically independent convenience kinetics

247307
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species: 658363

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initial amount: 5.0
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name: Gamma secretase

247331
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species: 658380

658380
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name: Notch TM

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is version of: CHEBI:36080
constant: false
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has only substance units: false
initial concentration: NaN
initial amount: 100.0
in compartment: 658326
name: DAPT

659082
type: Parameter
constant: true
value: 1.0

659094
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constant: true
value: 1.0

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constant: true
value: 1.0

659130
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constant: true
value: 1.0

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type: Parameter
constant: true
value: 1.0

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type: Parameter
constant: true
value: 1.0

659091
type: Parameter
constant: true
value: 1.0

W3 CDTF: Fri Apr 20 20:38:05 BST 2012

659121
type: Parameter
constant: true
value: 1.0

659070
type: Parameter
constant: true
value: 1.0

658908
type: Reaction
kinetic law: 247594
product: 247582
reactant: 247570
notes: mass action rate law for first order forward, first order reverse, reversible reactions, continuous scheme
fast: false
reversible: true

247582
type: SpeciesReference
stoichiometry: 1.0
species: 658464

247570
type: SpeciesReference
stoichiometry: 1.0
species: 658600

ORG:
  orgname: Rajiv Gandhi Centre for Biotechnology
n:
  given: KC
  family: Sivakumar

W3 CDTF: Wed Nov 02 14:54:21 GMT 2011

ORG:
  orgname: EMBL-EBI
n:
  given: Vijayalakshmi
  family: Chelliah